cDNA of both the insulin and the IGF-I receptor have been cloned and sequenced by two groups and successful expression in mammalian cells of biologically active receptors was readily achieved..sup.1 The receptors are glycoproteins which consist of a heterotetramer of two extracellular .alpha. subunits and two transmembrane .beta. subunits which have both an extracellular and an intracellular portion. The .alpha. subunits contain the insulin binding site. It is plausible that each .alpha. subunit may contain one binding site. The insulin receptor has homology with the insulin-like growth factor I (IGF I) receptor and with the epidermal growth factor receptor, the human c-erb-2 oncogene, and the v-ros oncogene-encoded tyrosine kinase. FNT .sup.1 Ebina, et al. (1985) Cell 46:747-758; Ullrich, et al. Nature 313:756-761 (1985); Ullrich, et al., The Embo J. 5:2503-2512 (1986). Ebina and Ullrich utilize different sequence numbers. The Ullrich sequence numbers are used exclusively herein.
Knowledge of receptor structures is limited to the primary sequence deduced from cDNA cloning. This information has produced few clues as to the precise localization of the insulin or IGF-I binding domain on the .alpha. subunits, each of which contains more than 700 amino acid residues. Nor is definitive information of the secondary or tertiary structure of the receptors available.